Prolonged ethanol consumption has been found to lower the levels of polyunsaturated fatty acids especially, 20:4n6 (arachidonic acid) and 22:6n3 (docosahexaenoic acid), in plasma lipoproteins, erythrocytes, livers, brains, and the retinas of primates and felines maintained on low essential fatty acid diets (in the CNS, 22:6n3 is the principal fatty acid which decreased). The fatty acids, 20:4n6 and 22:6n3, are produced from the essential fatty acids (EFA), linoleate (18:2n6) and linolenate (18:3n3), respectively. A stable isotope gas chromatography-mass spectrometry (GC-MS) method is being used to examine the effects of ethanol on the production of polyunsaturated fatty acids in vivo. Since lipid peroxidation may play a particular role in the depletion of polyunsaturated fatty acids, the levels of 4-hydroxyalkenals and the 8-isoprostane-F(2)-alpha, in tissues are also being monitored using GC-MS procedures. In conjunction with metabolism studies, neural function at the level of the retina is being studied using electroretinography. Primates that have been consuming ethanol (on average 24% of energy) daily for four years have developed significant alcohol-induced liver pathology, including steatosis, inflammation, pericellular, and venular fibrosis. The levels of 20:4n6 and 22:6n3 decreased in plasma lipoproteins, erythrocytes, and liver phospholipids. In the brains there were lower levels of 22:6n3 and and a compensatory increase in 22:5n6 levels. In vivo EFA metabolism studies indicated that the uptake of 18:3n3 or 18:2n6 into the plasma was about the same in both controls and alcohol-exposed animals. Lipid peroxidation as evidenced by higher levels of 4-hydroxynonenal and 8-isoprostane-F(2)-alpha in the plasma appear to be a primary cause which leads to decreases in tissue polyunsaturated fatty acids. Neural processes related to visual function were also effected since there were significant alterations in the electroretinograms of alcohol-exposed primates compared to controls.